Flexibases: A way to enhance the use of molecular docking methods

Summary

Specially expanded databases containing three-dimensional structures are created to enhance the utility of docking methods to find new leads, i.e., active compounds of pharmacological interest. The expansion is based on the automatic generation of a set of maximally dissimilar conformations. The ligand receptor system of methotrexate and dihydrofolate reductase is used to demonstrate the feasibility of creating flexibases and their utility in docking studies.

Still, W.C., Mohamadi, F., Richards, N.J.G., Guida, W.C., Liskamp, R., Lipton, M., Caufield, C., Chang, G. and Hendrickson, T., Batchmin and batch-oriented modeling program working under MACROMODEL, Version 4.0, Department of Chemistry, Columbia University, New York, NY. The Allinger MM2 force field, as supplied with Batchmin, was used with the following supplemental parameters: N2*C2*N2 angles were set at 128° and 0.96 mdyn/rad2; *N2* angles were set at 123° and 0.7 mdyn/rad2; and C2*C2-C3-N2 and O3-C2-C3-N2 torsions both had their V2 terms set at 0.7 kcal/mol. A constant dielectric of 1.0 was used.Google Scholar